Elevated soluble adhesion molecules in women with pre-eclampsia

Abstract

Objective: The purpose of the present study was to evaluate the clinical significance of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) for endothelial cell activation in pre-eclampsia. Therefore, we determined and compared the correlations between these cytokines and circulating adhesion molecules in the sera of pre-eclamptic pregnant women, normotensive pregnant women and nonpregnant women. Methods: The soluble adhesion molecules VCAM-1, ICAM-1, E-selectin, and P-selectin were determined in the serum of 38 pre-eclamptic pregnant women and 40 normotensive pregnant and nonpregnant controls using ELISA-techniques. We correlated these serum concentrations with the serum levels of TNF-α and IL-1β, respectively, also determined by ELISA. Results: Elevated serum levels of VCAM-1 and E-selectin could be detected in pre-eclamptic patients, with and without HELLP-syndrome. In contrast, no increased serum concentration of ICAM-1, P-selectin, TNF-α and IL-1β were found in these patients. While significant correlation between VCAM-1 and E-selectin could be determined (r=0.604; p<0.001) no unambiguous correlations, however, were found between TNF-α or between IL-1β and the examined adhesion molecules or the selectins. Conclusions: In contrast to in vitro investigations on cultured umbilical vein endothelium, our experimental results indicate that the cytokines TNF-α and IL-1β can not explain endothelial cell activation, and that their measurement in serum is not useful for the detection of pre-eclampsia.

Introduction

In pre-eclampsia endothelial dysfunction is of major significance [1]. Prerequisites for this situation can be an activation of endothelial cells by adhesion molecules accompanied by adhesion of leukocytes on the endothelial surface and subsequent transmigration of the leukocytes into the perivascular tissue [2], [3].

Increases in the serum concentrations of vascular adhesion molecule-1 (VCAM-1) [4], [5], [6], intercellular adhesion molecule-1 (ICAM-1) [5], [6], [7], [8], E-selectin [6], and P-selectin [9] have been detected as markers of an endothelial cell activation.

In vitro, cultured human endothelial cells can be stimulated to express VCAM-1, ICAM-1, and E-selectin as well as P-selectin by tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) [10], [11].

In contrast to the above-mentioned in vitro findings, the role of cytokines, such as TNF-α and IL-1β for endothelial cell activation has not been clearly elucidated, especially since different results of these cytokines have been found in the sera of pre-eclamptic pregnant women [12], [13], [14], [15], [16], [17]. Several authors found elevated TNF-α serum levels in patients with pre-eclampsia [15], [17] or HELLP-syndrome [13] and concluded that this cytokine plays an active role in mediating the endothelial damage [13]. Vince et al. believe that endothelial dysfunction could arise for this excessive release of TNF-α into the circulation [17].

The objective of the present work was thus to comparatively investigate the correlations between TNF-α and IL-1β and circulating adhesion molecules in the sera of pre-eclamptic pregnant women and therefore, to evaluate their clinical significance for endothelial activation. These data were compared with serum levels of normotensive pregnant and nonpregnant women.